Preterm birth (PTB), defined as delivery before 37 wk of gestation, is a significant public health problem accounting for 70% of perinatal mortality and nearly half of long-tenn neurological morbidity (Goldenberg et al., (2000) N. Engl. J. Med. 342:1500-1507). The PTB rate in the United States is about 12% of all live deliveries, affecting a half-million babies and costing billions of dollars annually (Andrews et al., (2000) Am. J. Perinatol. 17:357-365).
Research has shown that intrauterine infections are highly prevalent among women who give birth prematurely (Chaim et al., (1992) Arch. Gynecol. Obstet. 259:51-58). The infecting organisms have been shown to originate from the lower genital tract and invade the pregnant uterus via an ascending mechanism or come from other parts of the body, such as the oral cavity, and reach the uterus through hematogenous transmission (Hill et al., (1998) Ann. Periodontol. 3:222-232).
The recent identification of an uncultivated oral species, Bergeyella species, in the amniotic fluid from a pregnancy complicated by premature delivery provides direct evidence in support of the oral-utero transmission (Han et al., (2006) J. Clin. Microbiol. 44:1475-1483). The Bergeyella species identified in amniotic fluid matched that found in the woman's dental plaque but was undetected in her vaginal sample (Hill et al., (1998)).
Fusobacterium nucleatum is one of the most prevalent species associated with intrauterine infection (Hill et al., (1998); Altshuler et al., (1985) Arch. Pathol. Lab. Med. 109:739-743; Chaim and Mazor (1992) Arch. Gynecol. Obstet. 251:1-7; Hill et al., (1974) Infect. Immun. 9:599-603). It is a Gram-negative anaerobic oral species and an opportunistic human pathogen associated with various forms of periodontal disease. The organism can be isolated at a frequency of 10-30% from the amniotic fluid of women in preterm labor with intact membranes (Hill et al., (1993); Hill et al., (1998), Chaim et al., (1992); Cahill et al., (2005) Mol. Hum. Reprod. 11:761-766) and detected in 83% of PTB with premature rupture of membranes by PCR (Cahill et al., (2005)).
A causal relationship between F. nucleatum and adverse pregnancy outcome has been established in studies in mice. Hematogenous infection of pregnant mice by orally related F. nucleatum resulted in localized infections of the fetoplacental unit, leading to preterm and term stillbirths (Han et al., (2004) Infect. Immun. 72:2272-2279). The infections initiated at the decidua followed by spreading to the fetal membranes, amniotic fluid, and fetus, similar to the pattern observed in the ascending mechanism (Goldenberg et al., (2000), Han et al., (2004)). F. nucleatum is known to invade epithelial and endothelial cells in vitro (Han et al., (2005) J. Bacteriol. 187:5330-5340); its attachment and invasion of the endothelial cells have been observed in vivo in infected mouse placentas.